Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn - review on current management and outcome

Research into fetal development and medicin

Treated Unconventional Waters Combined with Different Irrigation Strategies Affect 1 H NMR Metabolic Profile of a Monovarietal Extra Virgin Olive Oil

none8noThe agricultural sector is facing a decrease in water supply and water quality at a global level and this is a problem that strictly affects all the Mediterranean olive growing areas. The aim of this work was to evaluate, for the first time, by NMR Spectroscopy and multivariate data analysis the metabolic profiling of the oils produced under different irrigation schemes. Arbosana olive oils were obtained from the use of saline reclaimed water (RW) and treated municipal wastewater (DW), combined with: full irrigation (FI) and regulated deficit irrigation (RDI). The results show a higher relative content of saturated fatty acids in EVOOs obtained from RDI strategy, regardless of the water source. Moreover, an increase in unsaturated fatty acids, a ω6/ω3 ratio content was observed in EVOOs obtained from RW when compared with DW water. Furthermore, the RW–RDI showed an increase in secoiridoid derivatives and hydroperoxides with respect to DW–RDI. A sustainable irrigation management, by combining a deficit irrigation strategy and saline reclaimed water source, could be crucial in order to overcome the problem of water scarcity and to guarantee the olive oil nutraceutical properties. The1 H NMR-based metabolomic approach proved a powerful and versatile tool for this specific investigation.openAngile F.; Vivaldi G.A.; Girelli C.R.; Del Coco L.; Caponio G.; Lopriore G.; Fanizzi F.P.; Camposeo S.Angile, F.; Vivaldi, G. A.; Girelli, C. R.; Del Coco, L.; Caponio, G.; Lopriore, G.; Fanizzi, F. P.; Camposeo, S

Current management of primary mitochondrial disorders in EU countries: the European Reference Networks survey

Background and purpose: Primary mitochondrial diseases (PMDs) are rare diseases for which diagnosis is challenging, and management and training programs are not well defined in Europe. To capture and assess care needs, five different European Reference Networks have conducted an exploratory survey. Methods: The survey covering multiple topics relating to PMDs was sent to all ERNs healthcare providers (HCPs) in Europe. Results: We have collected answers from 220 members based in 24/27 European member states and seven non-European member states. Even though most of the responders are aware of neurogenetic diseases, difficulties arise in the ability to deliver comprehensive genetic testing. While single gene analysis is widely available in Europe, whole exome and genome sequencing are not easily accessible, with considerable variation between countries and average waiting time for results frequently above 6 months. Only 12.7% of responders were happy with the ICD-10 codes for classifying patients with PMDs discharged from the hospital, and more than 70% of them consider that PMDs deserve specific ICD codes to improve clinical management, including tailored healthcare, and for reimbursement reasons. Finally, 90% of responders declared that there is a need for further education and training in these diseases. Conclusions: This survey provides information on the current difficulties in the care of PMDs in Europe. We believe that the results of this survey are important to help rare disease stakeholders in European countries identify key care and research priorities

po 266 metabolic profiling of osteosarcoma cancer stem cells as tool to identify potential target for cancer therapy

Introduction Recently, several studies have highlighted the key role of cancer stem cells (CSC) in tumour initiation, metastasis, and relapses. The CSC pool generally exhibits higher resistance to conventional chemo-radiotherapy and a different cell metabolism. Aim of our study is to investigate the main metabolic differences in the human osteosarcoma stem-like cells (3ABOS) and differentiated osteosarcoma cells (MG63) to unveil new metabolic therapeutic targets. Material and methods Metabolic analyses were performed with Seahorse Bioanalyzer. Live cell imaging for ROS content, mitochondrial membrane potential and morphology, were performed by confocal microscopy by using DCF-DA, Mito-Tracker Red and NAO as selective probes, respectively. Protein expression was revealed by qPCR and western blot. Results and discussions Our results showed a significant reduction of the mitochondrial oxygen consumption rate in 3ABOS compared with MG63 cells. Next, we assessed the specific contributions of glucose, fatty acid and glutamine to the respiratory phenotype, unveiling larger reliance on oxidation of these three main fuels with a significant reduction in mitochondrial flexibility in 3ABOS. The lower OXPHOS is compensated by a shift in glucose metabolism demonstrated by increased extracellular acidification rate.These results were further supported by a significant reduction of 3ABOS proliferation in glucose shortage. According to this scenario, confocal microscopy highlighted reduced mitochondrial membrane potential, and increased ROS content in 3ABOS compared to MG63. Additionally, 3ABOS displayed a lower mitochondrial DNA amount associated with more elongated mitochondrial network confirmed by both live cell imaging and Mitofusin expression analysis. Moreover, members of the NADPH oxidases family resulted to be differently expressed in the two cell lines, thus suggesting a potential role of ROS mediated signalling in cancer cell phenotype. Conclusion Overall our results demonstrated that the oxidative metabolic phenotype hallmarks cancer biology. Further investigations are ongoing to define specific drugs acting on metabolic target and their effectiveness as a therapeutic approach

po 268 adipose derived mesenchymal stem cells microenvironment promotes the tumorigenic phenotype in triple negative breast cancer cell line

Introduction Breast cancer is one of the common cause of cancer-related deaths in women, and the vast majority of breast cancer-related deaths involve metastatic disease. Thus, an understanding of the molecular and cellular mechanism supporting tumour progression is essential for developing targeted treatments. Recently, several studies have recognised the critical role of the metabolic setting and of microenvironmental cues in tumour development and therapeutic responses. In the present study we investigated the tumor-stroma metabolic interplay in MDA-MB-231 (high metastatic) cultured with conditioned medium (CM) from mammary adipose tissue-derived mesenchymal stem cells (MSC) either under high (HG) and low glucose (LG) regimen. Material and methods Metabolic fluxes analyses were performed with Seahorse Bioanalyzer providing both mitochondrial respiratory activity, as oxygen consumption rate (OCR), and glycolysis-related extracellular acidification rate (ECAR). Live cell imaging for mitochondrial membrane potential Δψ m , was performed by confocal microscopy by using TMRE as selective probe. Cell migration was evaluated by scratch assay monitoring the wound's closure after 24 hour. Results and discussions Metabolic fluxes analysis showed that HG growth condition caused a significant reduction of OCR and ECAR in MDA cell line as well as in MSC. MDA grown in MSC-derived CM revealed a dampening of OCR and ECAR and this effect was attained irrespectively of the glucose concentration. Analysis of Δψ m showed a significant decrease only in MDA cultured with CM from HG-MSC. Intriguingly, in a specular setup MSC cultured with CM from theMDA, a significant reduction of ECAR, both in HG and LG was observed whereas OCR resulted to be strongly reduced only in HG. Our results would indicate a reciprocal interplay between the one of the most aggressive breast cancer cell line and MSC in rewiring the mitochondrial oxidative metabolism and likely the tumour phenotype. Consistently, in vitro scratch assay showed an increasing migration of MDA cultured with CM from MSC HG, thus suggesting a key role of MSC in facilitating cancer progression/invasiveness. Conclusion Our results strongly support the involvement of stromal MSC in tumour metabolism of malignant phenotypes. Further experiments are needed to define the factors released from MDA acting on MSC metabolism. Understanding these interactions is fundamental to develop therapeutic interventions addressing the MSC-tumour interaction

po 213 high glucose affects er breast cancer cell metabolism

Introduction In vitro high glucose (HG) level, mimicking hyperglycemia condition in vivo , has been reported to influence breast cancer cells growth, proliferation and survival suggesting glucose as being crucial for breast cancer progression and response to therapy in diabetic patients. Diabetes, in turn, might have a direct effect on breast cancer prognosis. This study investigated the impact of HG on MCF-7 breast cancer cell metabolism and phenotype. Material and methods MCF-7 breast cancer cell line were cultured in DMEM with high glucose (HG 25 mM) and low glucose (LG 5 mM). Metabolic fluxes analyses were performed with Seahorse Bioanalyzer. Live cell imaging for reactive oxygen species (ROS) content was performed by confocal microscopy by using DCF-DA as selective probe. Mitochondrial DNA (mtDNA) and protein expression were evaluated by qPCR and western blotting respectively. Results and discussions Using a metabolic fluxes analyses, we showed a significant reduction of the mitochondrial oxygen consumption rate (OCR) and glycolysis-related extracellular acidification rate (ECAR) in MCF-7 cultured in HG- as compared in LG-medium. According with these results, MCF-7 in HG displayed lower mtDNA amount and increased ROS level. Furthermore, the analysis of stemness markers revealed a significant upregulation of Nanog, Lin28 and Myc thus suggesting an increased stem-like phenotype due to growth in HG. Conclusion Overall our results indicate that glucose may foster breast cancer progression promoting stem cell-like phenotype strongly affecting the metabolic profile in MCF-7 cell line. Further investigations are ongoing to define the mechanism underlying the switch towards an undifferentiated state to be exploited as therapeutic target

Are fetal bilirubin levels associated with the need for neonatal exchange transfusions in hemolytic disease of the fetus and newborn?

BACKGROUND: Fetal bilirubin is routinely measured at our center when taking a pretransfusion blood sample at intrauterine transfusions in hemolytic disease of the fetus and newborn. However, the clinical value of fetal bilirubin assessment is not well known, and the information is rarely used. We speculated that there could be a role for this measurement in predicting the need for neonatal exchange transfusion.OBJECTIVE: This study aimed to evaluate the predictive value of fetal bilirubin for exchange transfusions in severe hemolytic disease of the fetus and newborn.STUDY DESIGN: A total of 186 infants with Rh alloantibody-mediated hemolytic disease of the fetus and newborn treated with one or more intrauterine transfusions at the Leiden University Medical Center between January 2006 and June 2020 were included in this observational study. Antenatal and postnatal factors were compared between infants with and without exchange transfusion treatments. The primary outcome was the fetal bilirubin levels before the last intrauterine transfusion in relation to the need for exchange transfusion.RESULTS: In a multivariate logistic regression analysis, the fetal bilirubin level before the last intrauterine transfusions (odds ratio, 1.32; 95% confidence interval, 1.09-1.61 per 1 mg/dL) and the total number of intrauterine transfusions (odds ratio, 0.63; 95% confidence interval, 0.44-0.91 per intrauterine transfusion) were independently associated with the need for exchange transfusion. The area under the curve was determined at 0.71. A Youden index was calculated at 0.43. The corresponding fetal bilirubin level was 5 mg/dL and had a sensitivity of 79% and a specificity of 64%.CONCLUSION: A high fetal bilirubin level before the last intrauterine transfusion was associated with a high likelihood of neonatal exchange transfusion.DevelopmentImmunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Long-Term Neurodevelopmental Outcome of Monochorionic and Matched Dichorionic Twins

Contains fulltext : 79941.pdf (publisher's version ) (Open Access)BACKGROUND: Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years. METHODS: This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. FINDINGS: Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin. CONCLUSIONS: There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates

Clinical epidemiolog

Treatment and outcome of 370 cases with spontaneous or post-laser twin anemia-polycythemia sequence managed in 17 fetal therapy centers.

OBJECTIVE: To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post-laser twin anemia-polycythemia sequence (TAPS). METHODS: This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post-laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and < 1.0 MoM in the TAPS recipient. The following antenatal management groups were defined: expectant management, delivery within 7 days after diagnosis, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)), laser surgery and selective feticide. Cases were assigned to the management groups based on the first treatment that was received after diagnosis of TAPS. The primary outcomes were perinatal mortality and severe neonatal morbidity. The secondary outcome was diagnosis-to-birth interval. RESULTS: In total, 370 monochorionic twin pregnancies were diagnosed antenatally with TAPS during the study period and included in the study. Of these, 31% (n = 113) were managed expectantly, 30% (n = 110) with laser surgery, 19% (n = 70) with IUT (± PET), 12% (n = 43) with delivery, 8% (n = 30) with selective feticide and 1% (n = 4) underwent termination of pregnancy. Perinatal mortality occurred in 17% (39/225) of pregnancies in the expectant-management group, 18% (38/215) in the laser group, 18% (25/140) in the IUT (± PET) group, 10% (9/86) in the delivery group and in 7% (2/30) of the cotwins in the selective-feticide group. The incidence of severe neonatal morbidity was 49% (41/84) in the delivery group, 46% (56/122) in the IUT (± PET) group, 31% (60/193) in the expectant-management group, 31% (57/182) in the laser-surgery group and 25% (7/28) in the selective-feticide group. Median diagnosis-to-birth interval was longest after selective feticide (10.5 (interquartile range (IQR), 4.2-14.9) weeks), followed by laser surgery (9.7 (IQR, 6.6-12.7) weeks), expectant management (7.8 (IQR, 3.8-14.4) weeks), IUT (± PET) (4.0 (IQR, 2.0-6.9) weeks) and delivery (0.3 (IQR, 0.0-0.5) weeks). Treatment choice for TAPS varied greatly within and between the 17 fetal therapy centers. CONCLUSIONS: Antenatal treatment for TAPS differs considerably amongst fetal therapy centers. Perinatal mortality and morbidity were high in all management groups. Prolongation of pregnancy was best achieved by expectant management, treatment by laser surgery or selective feticide. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology